Test Catalog

Test Id : UGTFG

UDP-Glucuronosyltransferase 1A1 (UGT1A1), Full Gene Sequencing, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying individuals who are at increased risk of adverse drug reactions with drugs that are metabolized by UGT1A1, including irinotecan, atazanavir, nilotinib, pazopanib, and belinostat

 

Identifying individuals who are at risk of hyperbilirubinemia

 

Follow-up testing for individuals with a suspected UGT1A1 variant, who had negative TA repeat region testing

 

Establishing a diagnosis of Gilbert, Crigler-Najjar syndrome type I or type II

 

Establishing carrier status for Gilbert, Crigler-Najjar syndrome type I or type II

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This is a full gene sequencing test for UGT1A1 that includes the TA repeat region of the promoter and all intron/exon boundaries. Results are interpreted for the purposes of UGT1A1 drug metabolism and hereditary hyperbilirubinemia syndromes (Gilbert syndrome and Crigler-Najjar syndrome).

Highlights

This test screens for UGT1A1 gene variants associated with increased risk of adverse drug reactions when taking UGT1A1-metabolized drugs. These drugs include irinotecan, atazanavir, nilotinib, pazopanib, and belinostat

 

This test screens for UGT1A1 gene variants associated with congenital hyperbilirubinemia conditions including Gilbert syndrome, Crigler-Najjar syndrome type I and type II

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See UGT1A1 Test-Ordering Algorithm in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

UGT1A1 Full Gene Sequencing

Aliases
Lists additional common names for a test, as an aid in searching

Atazanavir

Belinostat

GNT1

Irinotecan

Irinotecan glucuronidation

Irinotecan metabolism

Nilotinib

Pazopanib

Phenol/Bilirubin

UDP-Glucuronosyltransferase

UDP-Glucosyltransferase 1

UGT1A1

Uracil Glucuronyl transferase

Uridine Diphosphate Glucosyltransferase 1

Crigler-Najjar Syndrome

Gilbert Syndrome

Hyperbilirubinemia

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See UGT1A1 Test-Ordering Algorithm in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

If analysis of only the UGT1A1 promoter TA repeat region (*28, *36, *37 alleles) is desired, see U1A1Q / UDP-Glucuronosyl Transferase 1A1 TA Repeat Genotype, UGT1A1, Varies.

Shipping Instructions

If submitting microtube, place inside a larger tube or vial for transport.

Necessary Information

UGT1A1 Gene Testing Patient Information (T664) is recommended, but not required, to be filled out and sent with the specimen.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple whole blood EDTA tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.

 

Patient Preparation: A previous bone marrow transplant from an allogenic donor or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Adults: Lavender top (EDTA)

Pediatrics: Purple microtube

Specimen Volume:

Adults: 3 mL

Pediatrics: 1 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Container/Tube: Saliva Swab Collection Kit

Specimen Volume: One swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. UGT1A1 Gene Testing Patient Information (T664) is requested but not required. See Special Instructions.

3. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Oncology Test Request (T729)

-Therapeutics Test Request (T831)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 0.45 mL

Saliva: 1 swab

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying individuals who are at increased risk of adverse drug reactions with drugs that are metabolized by UGT1A1, including irinotecan, atazanavir, nilotinib, pazopanib, and belinostat

 

Identifying individuals who are at risk of hyperbilirubinemia

 

Follow-up testing for individuals with a suspected UGT1A1 variant, who had negative TA repeat region testing

 

Establishing a diagnosis of Gilbert, Crigler-Najjar syndrome type I or type II

 

Establishing carrier status for Gilbert, Crigler-Najjar syndrome type I or type II

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This is a full gene sequencing test for UGT1A1 that includes the TA repeat region of the promoter and all intron/exon boundaries. Results are interpreted for the purposes of UGT1A1 drug metabolism and hereditary hyperbilirubinemia syndromes (Gilbert syndrome and Crigler-Najjar syndrome).

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See UGT1A1 Test-Ordering Algorithm in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The UGT1A1 gene is part of a gene complex located on chromosome 2 that encodes several enzymes called uridine diphosphate (UDP)-glycuronosyl transferases. These enzymes perform a chemical reaction called glucuronidation, a major pathway that enhances the elimination of small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble metabolites that can be excreted from the body.

 

The UGT1A1 enzyme, primarily found in the liver, is responsible for the gluronidation of bilirubin, converting it from the toxic form of bilirubin (unconjugated bilirubin) to its nontoxic, water-soluble form (conjugated bilirubin). Genetic variants in UGT1A1 may cause reduced or absent UGT1A1 enzymatic activity, resulting in conditions associated with unconjugated hyperbilirubinemia including Gilbert syndrome and Crigler-Najjar syndromes types I and II.

 

Gilbert syndrome is the most common hereditary cause of increased bilirubin and is characterized by total serum bilirubin levels of 1 to 6 mg/dL. Gilbert syndrome is generally considered to be an autosomal recessive disorder, although autosomal dominant inheritance has been suggested in some cases.(1) Gilbert syndrome is caused by a 25% to 50% reduction in glucuronidation activity of the UGT1A1 enzyme and is characterized by episodes of mild intermittent jaundice and the absence of liver disease.

 

Crigler-Najjar syndromes types I and II (CN1 and CN2) are autosomal recessive disorders caused by more severe reductions in UGT1A1 glucuronidation activity. CN1 is the most severe form, with complete absence of enzyme activity and total serum bilirubin levels of 20 to 45 mg/dL. Infants with CN1 present with jaundice shortly after birth that persists thereafter.(2) CN2 is milder than CN1, with at least partial UGT1A1 activity and total serum bilirubin ranging from 6 to 20 mg/dL. Phenobarbital, a drug that induces synthesis of a number of hepatic enzymes, is effective in decreasing serum bilirubin levels by approximately 25% in patients with CN2; CN1 does not respond to phenobarbital treatment. If left untreated, the buildup of bilirubin in a newborn can cause bilirubin-induced brain damage, known as kernicterus. In addition to phenobarbital, treatments of CN may include phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate, and liver transplantation.

 

In addition to the role of UGT1A1 in bilirubin metabolism, this enzyme also plays a role in the metabolism of several drugs. UGT1A1 is involved in the metabolism of irinotecan, a topoisomerase I inhibitor. Irinotecan is a chemotherapy drug used to treat solid tumors including colon, rectal, and lung cancers. It is a prodrug that forms an active metabolite, SN-38. SN-38 is normally inactivated by conjugation with glucuronic acid followed by biliary excretion into the gastrointestinal tract. If UGT1A1 activity is impaired or deficient, SN-38 fails to become conjugated with glucuronic acid, increasing the concentration of SN-38. This can result in severe neutropenia. The combination of neutropenia with diarrhea can be life-threatening.(3,4)

 

Additional drugs have also been associated with an increased risk for adverse outcomes in patients with reduced UGT1A1 enzyme activity. The FDA drug labels for nilotinib, pazopanib, and belinostat all contain warnings for an increased risk (incidence) of adverse outcomes in patients who have UGT1A1 variants associated with reduced activity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) released guidelines for atazanavir treatment, indicating that patients with homozygous UGT1A1 alleles associated with reduced activity or decreased expression should consider an alternate medication due to a significant risk for developing hyperbilirubinemia (jaundice).

 

The UGT1A1 gene maps to chromosome 2q37 and contains 5 exons. In this assay, the promoter, exons, and exon-intron boundaries are assessed for variants.(5)

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided that includes assessment of risk for UGT1A1-associated adverse drug reactions as well as interpretation for hyperbilirubinemia syndromes.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell, a pretransplant DNA specimen is recommended for testing.

 

UGT1A1 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's UGT1A1 status.

 

Absence of a detectable gene variant does not rule out the possibility that the patient may have a genetic cause for increased unconjugated bilirubin.

 

Rare variants exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Innocenti F, Grimsley C, Das S, et al: Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics. 2002;12:725-733. doi: 10.1097/00008571-200212000-00006

2. Costa E, Vieira E, Martins M, et al: Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes. Blood Cells Mol Dis. 2006;36:91-97. doi: 10.1016/j.bcmd.2005.09.002

3. Goetz MP, Safgren S, Goldberg RM, et al: A phase I dose escalation study of irinotecan (CPT-11), oxaliplatin (Oxal), and capecitabine (Cap) within three UGT1A1 TA promoter cohorts (6/6, 6/7, and 7/7). ASCO 2005 ASCO Annual Meeting Abstract No: 2014

4. NDA 20-571/S-024/S-027/S-028. Camptosar (Irinotecan HCL) Final Label. July 21, 2005. Pfizer

5. Kitagawa C, Ando M, Ando Y, et al: Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity. Pharmacogenet Genomics. 2005;15:35-41. doi: 10.1097/01213011-200501000-00006

6. Guilemette C: Pharmacogenomics of human UDP-glucuronosyltransferase enzymes. Pharmacogenomics J. 2003;3:136-158

7. Gammal R, Court M, Haidar C, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for UGT1A1 and atazanavir prescribing. Clin Pharmacol Ther. 2015 doi: 10.1002/cpt.269

8. Shibata T, Minami Y, Mitsuma A, et al: Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia. Int J Clin Oncol. 2014;19:391-396. doi: 10.1007/s10147-013-0562-5

9. US Food and Drug Administration, Pharmacogenomic Biomarkers in Drug Labeling. Accessed November 2015. Available at www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm

10. UDP-Glucuronosyltransferase Alleles Nomenclature page. Accessed March 2018. Available at www.pharmacogenomics.pha.ulaval.ca/ugt-alleles-nomenclature/

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Genomic DNA is extracted from whole blood. The UGT1A1 gene is amplified by polymerase chain reaction (PCR). The PCR product is then purified and sequenced in both directions using fluorescent dye-terminator chemistry. Sequencing products are separated on an automated sequencer and trace files analyzed for sequence variants in the exons and intron/exon boundaries using variant detection software and visual inspection.(Skierka J, O'Kane D: UDP-glucuronosyltransferase 1A1 and the glucuronidation in oncology applications and hyperbilirubinemia. In: Grody WW, Nakamura RM, Kiechle FL, Strom CM, eds. Molecular Diagnostics: Techniques and Applications for the Clinical Laboratory. Academic Press; 2010:409-420)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Tuesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

7 to 14 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood/Saliva Swab: 2 weeks; Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81404

LOINC® Information

Test Id Test Order Name Order LOINC Value
UGTFG UGT1A1 Full Gene Sequencing 93844-9
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
91972 Result Summary 50397-9
91977 TA Repeat Result 95143-4
BA0266 Full Gene Sequence Result 82939-0
91993 Interpretation 69047-9
92007 Additional Information 48767-8
92008 Method 85069-3
92009 Disclaimer 62364-5
92010 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports